83 research outputs found

    Paleogeographic Interpretation of a Peat Layer at Torson di Sotto (Lagoon of Venice, Italy)

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    Ein 3,3 m langer Kern aus dem zentralen Bereich der Lagune von Venedig enthielt eine Torflage zwischen 1,3 und 2,0 m unter dem mittleren Meeresspiegel. Pollenanalysen zeigen ein Vorherrschen von Quercus und Alnus und eine transgressive Phase an: der untere Teil des Torfes (nach 14C-Daten 1730±80 v.h.) ist in einem Süßwasser-Environment gebildet worden, der obere Teil (nach 14C-Daten 1140 + 80 v.h.) in einem brackischen. Foraminiferenanalysen zeigen an, daß der Transgression eine Regression vorangegangen ist. Die gesamte Abfolge enthält von unten nach oben (Abb. 3): (1) ein oligohalines bis mesohalines Environment (von —3,3 bis —2,5 m) mit sehr zahlreichen Foraminiferen; (2) ein Süßwasser-Environment (von —2,5 bis —2,0 m); (3) die 0,7 m mächtige Torflage, die fortschreitend brackisch wird; (4) ein mesohalines Environment (oberhalb —1,3 m).Korrelationen mit benachbarten Lokalitäten (Abb. 1) weisen darauf hin, daß vergleichbare Erscheinungen zu gleicher Zeit im Zentralteil der Lagune, aber nicht in ihrem Nordteil, aufgetreten sind. Diese Regressions-Transgressions-Abfolge wird auf eine Periode erhöhter Niederschläge um das Ende der Römerzeit zurückgeführt, die zur Überflutung und zu einer Verlagerung des Laufes zahlreicher Flüsse geführt hat; dabei ist das ökologische Gleichgewicht dieses Marschengebietes zeitweilig verändert worden. Im Verlauf der vergangenen 100 Jahre hat sich die Transgression beschleunigt, überwiegend infolge anthropogener Eingriffe. Die „Barene" werden jetzt erodiert und verschwinden rasch (Abb. 2). Sie werden durch weite Meerwasserbecken eingenommen.researc

    Pre-transplant CD45RC expression on blood T cells differentiates patients with cancer and rejection after kidney transplantation

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    Background Biological biomarkers to stratify cancer risk before kidney transplantation are lacking. Several data support that tumor development and growth is associated with a tolerant immune profile. T cells expressing low levels of CD45RC preferentially secrete regulatory cytokines and contain regulatory T cell subset. In contrast, T cells expressing high levels of CD45RC have been shown to secrete proinflammatory cytokines, to drive alloreactivity and to predict acute rejection (AR) in kidney transplant patients. In the present work, we evaluated whether pre-transplant CD45RClow T cell subset was predictive of post-transplant cancer occurrence. Methods We performed an observational cohort study of 89 consecutive first time kidney transplant patients whose CD45RC T cell expression was determined by flow cytometry before transplantation. Post-transplant events including cancer, AR, and death were assessed retrospectively. Results After a mean follow-up of 11.1±4.1 years, cancer occurred in 25 patients (28.1%) and was associated with a decreased pre-transplant proportion of CD4+CD45RChigh T cells, with a frequency below 51.9% conferring a 3.7-fold increased risk of post-transplant malignancy (HR 3.71 [1.24–11.1], p = 0.019). The sensibility, specificity, negative predictive and positive predictive values of CD4+CD45RChigh<51.9% were 84.0, 54.7, 89.8 and 42.0% respectively. Confirming our previous results, frequency of CD8+CD45RChigh T cells above 52.1% was associated with AR, conferring a 20-fold increased risk (HR 21.7 [2.67–176.2], p = 0.0004). The sensibility, specificity, negative predictive and positive predictive values of CD8+CD45RChigh>52.1% were 94.5, 68.0, 34.7 and 98.6% respectively. Frequency of CD4+CD45RChigh T cells was positively correlated with those of CD8+CD45RChigh (p<0.0001), suggesting that recipients with high AR risk display a low cancer risk. Conclusion High frequency of CD45RChigh T cells was associated with AR, while low frequency was associated with cancer. Thus, CD45RC expression on T cells appears as a double-edged sword biomarker of promising interest to assess both cancer and AR risk before kidney transplantation

    Arabidopsis A BOUT DE SOUFFLE is a putative mitochondrial transporter involved in photorespiratory metabolism and is required for meristem growth at ambient CO2 levels

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    Photorespiratory metabolism is essential in all oxygenic photosynthetic organisms. In plants, it is a highly compartmentalized pathway that involves chloroplasts, peroxisomes, mitochondria and the cytoplasm. The metabolic pathway itself is well characterized, and the enzymes required for its function have been identified. However, very little information is available on the transport proteins that catalyze the high metabolic flux between the involved compartments. Here we show that the A BOUT DE SOUFFLE (BOU) gene, which encodes a mitochondrial carrier, is involved in photorespiration in Arabidopsis. BOU was found to be co-expressed with photorespiratory genes in leaf tissues. The knockout mutant bou-2 showed the hallmarks of a photorespiratory growth phenotype, an elevated CO2 compensation point, and excessive accumulation of glycine. Furthermore, degradation of the P-protein, a subunit of glycine decarboxylase, was demonstrated for bou-2, and is reflected in strongly reduced glycine decarboxylase activity. The photorespiration defect in bou-2 has dramatic consequences early in the seedling stage, which are highlighted by transcriptome studies. In bou-2 seedlings, as in shm1, another photorespiratory mutant, the shoot apical meristem organization is severely compromised. Cell divisions are arrested, leading to growth arrest at ambient CO2. Although the specific substrate for the BOU transporter protein remains elusive, we show that it is essential for the function of the photorespiratory metabolism. We hypothesize that BOU function is linked with glycine decarboxylase activity, and is required for normal apical meristems functioning in seedlings

    Expression of Constitutively Active CDK1 Stabilizes APC-Cdh1 Substrates and Potentiates Premature Spindle Assembly and Checkpoint Function in G1 Cells

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    Mitotic progression in eukaryotic cells depends upon the activation of cyclin-dependent kinase 1 (CDK1), followed by its inactivation through the anaphase-promoting complex (APC)/cyclosome-mediated degradation of M-phase cyclins. Previous work revealed that expression of a constitutively active CDK1 (CDK1AF) in HeLa cells permitted their division, but yielded G1 daughter cells that underwent premature S-phase and early mitotic events. While CDK1AF was found to impede the sustained activity of APC-Cdh1, it was unknown if this defect improperly stabilized mitotic substrates and contributed to the occurrence of these premature M phases. Here, we show that CDK1AF expression in HeLa cells improperly stabilized APC-Cdh1 substrates in G1-phase daughter cells, including mitotic kinases and the APC adaptor, Cdc20. Division of CDK1AF-expressing cells produced G1 daughters with an accelerated S-phase onset, interrupted by the formation of premature bipolar spindles capable of spindle assembly checkpoint function. Further characterization of these phenotypes induced by CDK1AF expression revealed that this early spindle formation depended upon premature CDK1 and Aurora B activities, and their inhibition induced rapid spindle disassembly. Following its normal M-phase degradation, we found that the absence of Wee1 in these prematurely cycling daughter cells permitted the endogenous CDK1 to contribute to these premature mitotic events, since expression of a non-degradable Wee1 reduced the number of cells that exhibited premature cyclin B1oscillations. Lastly, we discovered that Cdh1-ablated cells could not be forced into a premature M phase, despite cyclin B1 overexpression and proteasome inhibition. Together, these results demonstrate that expression of constitutively active CDK1AF hampers the destruction of critical APC-Cdh1 targets, and that this type of condition could prevent newly divided cells from properly maintaining a prolonged interphase state. We propose that this more subtle type of defect in activity of the APC-driven negative-feedback loop may have implications for triggering genome instability and tumorigenesis

    Systematic identification of functional modules and cis-regulatory elements in Arabidopsis thaliana

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    <p>Abstract</p> <p>Background</p> <p>Several large-scale gene co-expression networks have been constructed successfully for predicting gene functional modules and cis-regulatory elements in Arabidopsis (<it>Arabidopsis thaliana</it>)<it>.</it> However, these networks are usually constructed and analyzed in an <it>ad hoc</it> manner. In this study, we propose a completely parameter-free and systematic method for constructing gene co-expression networks and predicting functional modules as well as cis-regulatory elements.</p> <p>Results</p> <p>Our novel method consists of an automated network construction algorithm, a parameter-free procedure to predict functional modules, and a strategy for finding known cis-regulatory elements that is suitable for consensus scanning without prior knowledge of the allowed extent of degeneracy of the motif. We apply the method to study a large collection of gene expression microarray data in Arabidopsis. We estimate that our co-expression network has ~94% of accuracy, and has topological properties similar to other biological networks, such as being scale-free and having a high clustering coefficient. Remarkably, among the ~300 predicted modules whose sizes are at least 20, 88% have at least one significantly enriched functions, including a few extremely significant ones (ribosome, <it>p</it> < 1E-300, photosynthetic membrane, <it>p</it> < 1.3E-137, proteasome complex, <it>p</it> < 5.9E-126). In addition, we are able to predict cis-regulatory elements for 66.7% of the modules, and the association between the enriched cis-regulatory elements and the enriched functional terms can often be confirmed by the literature. Overall, our results are much more significant than those reported by several previous studies on similar data sets. Finally, we utilize the co-expression network to dissect the promoters of 19 Arabidopsis genes involved in the metabolism and signaling of the important plant hormone gibberellin, and achieved promising results that reveal interesting insight into the biosynthesis and signaling of gibberellin.</p> <p>Conclusions</p> <p>The results show that our method is highly effective in finding functional modules from real microarray data. Our application on Arabidopsis leads to the discovery of the largest number of annotated Arabidopsis functional modules in the literature. Given the high statistical significance of functional enrichment and the agreement between cis-regulatory and functional annotations, we believe our Arabidopsis gene modules can be used to predict the functions of unknown genes in Arabidopsis, and to understand the regulatory mechanisms of many genes.</p
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